Chlamydia pneumoniae strain TWAR is a recently identified third species of Chlamydia that is unique based on serological, morphological, and DNA sequence homology (2,8; see the appended Citations). Humans are reportedly the sole host of C. pneumoniae.
Chiamydia are obligate intracellular bacteria. C. trachomatis and C. pneumotiiae are human pathogens, while C. psittaci is an animal pathogen (1,18) which may incidentally infect humans. C. pneumoniae causes respiratory infections, while C. trachomatis causes mainly oculogenital infections. The primary syndrome caused by infection of humans with the avian strains of C. psittaci is a pneumonia known as psittacosis or ornithosis. The major clinical manifestations of C. pneumoniae infection are pneumonia, bronchitis, pharyngitis, and sinusitis (3,11). C. pneumoniae infection has been associated with about 10% of community-acquired pneumonia. The infections are geographically widespread. Antibody prevalence studies have shown that virtually everyone is infected with C. pneumoniae at some time and that reinfection is common.
Ultrastructurally the TWAR elementary body has a unique pear-shape and a large periplasmic space, in contrast to the typically round elementary bodies of C. trachomatis and C. psittaci (2). In addition, small electron-dense bodies of undetermined function are seen in the peripiasmic space of TWAR elementary bodies. TWAR undergoes the same developmental cycle as other chiamydia, namely, infectious elementary bodies enter the cell and differentiate into reticulate bodies that undergo a series of divisions by binary fusion, with formation of reticulate bodies that mature to elementary bodies through an intermediate-form stage (2). Small outer membrane blebs are also sometimes seen.
U.S. Pat. No. 5,008,186, which is incorporated herein by reference, discloses methods for detecting C. pneumoniae, utilizing monoclonal antibodies directed against an antigenic determinant of the TWAR strain of chlamydia A representative monoclonal antibody for this purpose is produced by the cell line RR 402 which has been deposited at the American Type Culture Collection under accession No. HB 9109.
Sero-epidemiological studies have reported that TWAR infection may be widespread in the human population, and antibodies have been reported in 40 to 60% of adults. Antibodies are uncommon in children under 8 years of age, and the incidence rises sharply in older children and young adults, reaching a plateau in incidence in persons of greater than 30 years of age. TWAR is reportedly a common cause of pneumonia and certain other acute respiratory infections (3,40,41). Tetracyclines and macrolides are reportedly effective in treating Chlamydial pneumoniae respiratory infections.
Serological studies have reported an increase in antibody titers specific for C. pneumoniae and C. trachomatis in patients with myocarditis (3,12). In Finland, antibodies to TWAR were reported in 50% of patients with chronic coronary heart disease and in 68% of patients with acute myocardial infarction, as compared with an incidence of 17% in a control population (4,19). Thom et al. 1991 (5) reported results of a case-control study in which a relative risk of 2.0 for coronary artery disease was recorded among subjects with high titers of anti-TWAR IgG antibodies, when compared with control subjects having low titers of anti-TWAR and based on angiographically diagnosed coronary artery disease.
International Patent Publication No. WO 90/00061 describes methods for the treatment and diagnosis of coronary heart disease. This disclosure is based on the foundation that chiamydial infections, especially Chlamydia TWAR infections, play a significant role in the pathogenesis of coronary heart disease. The disclosed methods involve drug treatment and screening of or testing for presence of chlamydia or chiamydial antibodies. Also disclosed are pharmaceutical preparations for treating chiamydial infections in coronary heart disease.
Thus, a tenuous linkage between the presence of antibodies to Chlamydia pneumoniae and coronary heart disease has been suggested. However, the presence of circulating antibodies in such a large proportion of the human population is problematic for monitoring either the course or extent of a chlamydial infection, i.e., because the presence of antibodies is only indicative of an encounter sometime in life with an antigen. No evidence of chlamydial infection of heart or vascular tissue has previously been reported.